ABCMdb

PMID: 22039929

Valdameri G, Pereira Rangel L, Spatafora C, Guitton J, Gauthier C, Arnaud O, Ferreira-Pereira A, Falson P, Winnischofer SM, Rocha ME, Tringali C, Pietro AD
Methoxy stilbenes as potent, specific, untransported, and noncytotoxic inhibitors of breast cancer resistance protein.
ACS Chem Biol. 2012 Feb 17;7(2):322-30. doi: 10.1021/cb200435y. Epub 2011 Nov 11., [PubMed]

Sentences

No. Mutations Sentence Comment

34 ABCG2 p.Arg482Thr (25% and 10%, respectively), in agreement with other data published for compound 9.31 Rhodamine 123 efflux could also be studied using the R482T ABCG2 mutant: a maximum of 75% inhibition was then obtained at 10-20 μM, with an IC50 value of 0.45 μM (Figure 1B). Login to comment 46 ABCG2 p.Arg482Thr Inhibition of rhodamine 123 efflux in HEK293 cells transfected by either wild-type ABCB1 or R482T ABCG2 constructs. Login to comment 50 ABCG2 p.Arg482Thr (B) Effects of compound 9 (○) and GF120918 (■) on R482T-ABCG2-mediated efflux. Login to comment 71 ABCG2 p.Arg482Thr The interaction at this transport site was more sensitive to the R482T mutation than the interaction at the ABCG2-specific site, as monitored here by the relative loss in efficiency against rhodamine 123 and mitoxantrone efflux.26 Methoxy stilbenes probably bind to the same site as 6-prenylchrysin, since both types of ABCG2-specific inhibitors display the same partial inhibition (around 75%), possibly due to their rather small size. Login to comment 128 ABCG2 p.Arg482Thr All cells were maintained in Dulbecco`s modified Eagle`s medium (DMEM high glucose), supplemented with 10% fetal bovine serum (FBS), 1% penicilin/streptomycin, and drug supplemented in some cases with either 0.75 mg mL-1 G418 (HEK293-pcDNA3.1, HEK293-R482 or R482T), 2 mg mL-1 G418 (HEK293-MDR1), or 5 μM etoposide (HEK293-MRP1). Login to comment 129 ABCG2 p.Arg482Thr ABCG2- and ABCB1-Mediated Drug Transport. HEK293 cells were seeded at a density of 1 × 105 cells/well into 24-well culture plates and, after 48 h, exposed to 10 μM mitoxantrone (HEK293-R482 and HEK293-MDR1 cells) or 10 μM rhodamine 123 (HEK293-R482T and HEK293-MDR1 cells) for 30 min at 37 °C, in the absence or presence of compounds at various concentrations. Login to comment 132 ABCG2 p.Arg482Thr The Hill number of mitoxantrone efflux in HEK293 cells transfected by either wild-type ABCG2 or R482T ABCG2 contructs was determined from the curves (sigmoidal -3 parameters) fitted in the SigmaPlot 11.0 software and calculated by the equation f = axb /(cb + xb ), where b is the Hill number. Login to comment